Asymmetric aldol additions: Use of titanium tetrachloride and (-)-sparteine for the soft enolization of N-acyl oxazolidinones, oxazolidinethiones, and thiazolidinethiones

Asymmetric aldol additions using chlorotitanium enolates of N-acyloxazolidi none, oxazolidinethione, and thiazolidinethione propionates proceed with hi gh diastereoselectivity for the Evans or non-Evans syn product depending on the nature and amount of the base used. With 1 equiv of titanium tetrachlo ride and 2 equiv of (-)-sparteine as the base or 1 equiv of(-)-sparteine an d 1 equiv of N-methyl-2-pyrrolidinone, selectivities of 97:3 to >99:1 were obtained for the Evans syn aldol products using N-propionyl oxazolidinones, oxazolidinethiones, and thiazolidinethiones. The non-Evans syn aldol adduc ts are available with the oxazolidinethione and thiazolidinethiones by alte ring the Lewis acid/amine base ratios. The change in facial selectivity in the aldol additions is proposed to be a result of switching of mechanistic pathways between chelated and nonchelated transition states, The auxiliarie s can be reductively removed or cleaved by nucleophilic acyl substitution. Iterative aldol sequences with high diastereoselectivity can also be accomp lished.